NM_000611.6:c.67+2177G>A

Variant names:

• chr11-33720202-C-T
• rs12272807
• NM_000611.6:c.67+2177G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000611.6(CD59):​c.67+2177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,250 control chromosomes in the GnomAD database, including 1,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1191 hom., cov: 33)
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 6 publications found

Genes affected

CD59 (HGNC:1689): (CD59 molecule (CD59 blood group)) This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

CD59 Gene-Disease associations (from GenCC):

• primary CD59 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000284969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD59	NM_000611.6	c.67+2177G>A		intron_variant	Intron 2 of 3	ENST00000642928.2	NP_000602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD59	ENST00000642928.2	c.67+2177G>A		intron_variant	Intron 2 of 3		NM_000611.6	ENSP00000494884.1
ENSG00000284969	ENST00000534312.5	c.67+2177G>A		intron_variant	Intron 1 of 3	3		ENSP00000432362.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17875 AN: 152134 Hom.: 1186 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.118 AC: 17892 AN: 152250 Hom.: 1191 Cov.: 33 AF XY: 0.117 AC XY: 8694 AN XY: 74436

African (AFR) AF: 0.166 AC: 6909 AN: 41544

American (AMR) AF: 0.0645 AC: 986 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5178

South Asian (SAS) AF: 0.123 AC: 591 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1071 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0984 AC: 6696 AN: 68018

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.104 Hom.: 188

Bravo AF: 0.117

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.74
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12272807; hg19: chr11-33741748;